National Institute of Oncology

The aim of the study was to comprehensively characterize the population of hypertrophic cardiomyopathy (HCM) patients in Poland in 2016-2021, including the analysis of annual incidence, prevalence, comorbidities, and therapeutic paths. A population-based cross-sectional study was conducted using data from the Polish National Health Fund database. The analysis included a registered annual incidence and prevalence rates, mortality, prognosis, and data on patients pathways in the healthcare system. In 2016, the registered annual incidence of HCM diagnosis in Poland was 1,494 cases (3.89/100,000), decreasing to 808 cases (2.11/100,000) in 2021. Despite the decline in new diagnoses, the registered prevalence of HCM increased from 13,271 cases (34.53/100,000) in 2016 to 13,880 cases (36.23/100,000) in 2021, indicating improved patient survival. Annual mortality rose from 824 deaths (2.14/100,000) in 2016 to 1,022 deaths (2.67/100,000) in 2021, with the highest mortality observed in older adults (60+ years). The study highlights significant underdiagnosis of HCM in Poland. Mortality in HCM population remains high, underscoring the need for improvement in earlier detection and comprehensive care strategies in Polish healthcare system.

In this study, we aimed to compare metabolomic profiles, biodistribution, and detoxification patterns of the novel SN-38 derivative NMe with irinotecan (IR), and to identify NMe-specific metabolites to evaluate its preclinical pharmacokinetic advantages. In vivo ADME studies were conducted for NMe, a 9-aminomethyl SN-38 derivative, and IR following a single intraperitoneal dose of 40 mg/kg in mice. Additionally, ADMET properties were predicted using ADMETlab and SwissADME tools for comparison. Levels of NMe and irinotecan absorbed into plasma, distributed to tissues, and metabolized were monitored in liver, lung, spleen, kidney, and stool samples at 15, 30, and 60 min post-administration. Tissue extracts were analysed using high-performance liquid chromatography (HPLC), liquid chromatography-electrospray ionization quadrupole time-of-flight-tandem mass spectrometry (LC-ESI-QTOF-MS), and nuclear magnetic resonance (NMR) techniques after lyophilization and reconstitution. We compared the metabolomic profiles of irinotecan and NMe. We identified and confirmed NMe-specific metabolites, including 9-CH2-S-cysteine conjugate, 9-CH2OH, and NMe-formyl. Notably, novel irinotecan metabolites (IR-OH and IR-ΔE) were detected in small amounts in kidney samples. In some cases, two literature-known photodegradation products of irinotecan were present. NMe was found to quickly metabolize with different distribution to tissues, significantly greater to kidney and liver. Two SN-38 glucuronides, SN-38G(α) and SN-38G(β), were detected corresponding to α- and β-anomers. Where it was possible, NMe, IR and SN-38 were quantified using external calibration curves. In IR group, controlled and prolonged release of SN-38 was confirmed in all samples, yet SN-38G was observed in minority only in plasma, kidney, or lungs. In NMe groups, great relative amounts of SN-38 and SN-38G were detected. Greater content of SN-38G in NMe group than in irinotecan is expected to contribute to modulation and alleviation of some side effects in irinotecan-involved therapies, such as gastrointestinal toxicities (GIT). NMe shows a distinct metabolic profile characterized by rapid biotransformation, higher systemic glucuronidation of SN-38, and formation of unique metabolites, suggesting a potentially wider therapeutic window and reduced toxicity compared with IR.

Introduction. The purpose of this study is to evaluate the influence of the neutrophil-lymphocyte ratio (NLR) and the systemic immune-inflammation index (SII) on the survival of EGFR -mutated vs. ALK / ROS rearranged non-small cell lung cancer (NSCLC). Material and methods. Only patients with EGFR -mutated (N = 64) or ALK / ROS -rearranged (N = 29) metastatic NSCLC treated with tyrosine kinase inhibitors (TKI) were enrolled. The Cox regression model was used to assess the impact of selected variables on survival, including the influence of NLR and SII. Results. The NLR and SII did not significantly influence survival in patients with EGFR-mutated NSCLC. On the contrary, NLR and SII significantly influenced survival in patients with ALK / ROS rearranged NSCLC. Conclusions. Despite previously accomplished studies on this subject, the influence of inflammatory markers on the outcome of patients treated with TKI deserves further attention. Hypothesized herein is that NLR and SII may be helpful in stratification of patients with ALK / ROS rearrangements for clinical trials on combinations of immune checkpoint inhibitors (ICI) and TKI.

Abstract Background: In the KEYNOTE-522 study (NCT03036488), neoadjuvant pembrolizumab (pembro) plus chemotherapy (chemo) followed by adjuvant pembro plus chemo significantly improved pathological complete response (pCR), event-free survival, and OS compared with placebo (pbo) plus chemo in participants (pts) with early-stage TNBC. Following neoadjuvant therapy, the estimated treatment difference in pCR for pembro plus chemo vs pbo plus chemo was 13.6% (95% CI, 5.4%‒21.8%; P < 0.001) at the first interim analysis (N=602). Although pCR provides a definitive indicator of neoadjuvant treatment success, other measures, such as RECIST v1.1 and functional tumor volume (FTV), may offer an earlier signal of therapeutic activity. This prespecified exploratory analysis evaluated associations of pCR with ORR at different time points per MRI by RECIST v1.1 and FTV by blinded independent central review. Methods: Pts with previously untreated TNBC (stage T1c N1-N2 or T2-T4 N0-N2) were randomized 2:1 to neoadjuvant pembro 200 mg Q3W or pbo, each with 4 cycles of paclitaxel plus carboplatin (treatment 1) then with 4 cycles of doxorubicin or epirubicin plus cyclophosphamide (treatment 2). After definitive surgery, pts received adjuvant pembro or pbo for 9 cycles or until recurrence/unacceptable toxicity. Breast MRI was performed for consenting pts at screening and after neoadjuvant treatments 1 and 2. Responders were defined as pts who achieved CR or PR per RECIST v1.1 by blinded independent central radiology review. The subgroup analyses population included the randomized pts who signed MRI consent and had baseline values by central radiology review. Results: At data cutoff (March 23, 2021), MRI subgroup analyses included 162 pts (pembro plus chemo, n = 97; pbo plus chemo, n = 65). After treatment 1, ORR per RECIST v1.1 was 91.8% for pembro plus chemo vs 84.6% for pbo plus chemo, while ORR per MRI FTV was 96.9% vs 93.8%. After treatment 2, ORR per RECIST v1.1 was 82.5% vs 90.8%, and ORR per MRI FTV was 84.5% vs 92.3% for pembro plus chemo and pbo plus chemo, respectively. In the post hoc exploratory analyses for pCR in the MRI subgroup, pCR rate (ypT0/Tis ypN0; 95% CI) was 62.9% (52.5%-72.5%) with pembro plus chemo vs 52.3% (39.5%-64.9%) with pbo plus chemo. Odds ratios (OR) for achieving pCR among pts with ORR per RECIST v1.1 or FTV across all patients (pembro plus chemo and pbo plus chemo combined) are shown in the Table. Conclusions: Across all pts (ie, for pembro plus chemo and pbo plus chemo combined), the odds of achieving pCR were higher among pts who had an objective response per either RECIST v1.1 or FTV. Citation Format: J. Cortés, R. Dent, H. McArthur, L. Pusztai, S. Kümmel, C. Denkert, J. O’Shaughnessy, P. A. Fasching, M. Untch, R. Tarnawaski, M. Mouret-Reynier, S. M. Stemmer, T. Foukakis, J. Boileau, C. Chung, M. Fernandez, J. A. Mejia, F. Beca, S. Hou, P. Schmid. Phase 3 study of neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab for early-stage TNBC: KEYNOTE-522 magnetic resonance imaging (MRI) subgroup analysis [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-07-24.

Abstract Background: The RxPONDER trial was a landmark study demonstrating that the 21-gene Oncotype DX (ODX) assay can help avoid unnecessary adjuvant chemotherapy in postmenopausal women with 1-3 positive nodes (N+) and an ODX recurrence score (RS) ≤25. However, N+ premenopausal women with RS≤25 showed a significant but variable benefit to adjuvant chemotherapy despite low or intermediate ODX RS. Current NCCN guidelines therefore recommend ODX only as a consideration in this subgroup, leaving risk-adapted decision-making unresolved. Ataraxis Breast (ATX) is a multi-modal artificial intelligence test that integrates morphological features extracted from standard H&E-stained slides with baseline clinical data. Here we validate the prognostic accuracy of ATX in four premenopausal N+ cohorts. Methods: 150 premenopausal HR+/HER2- node-positive cases were extracted from Providence Health (n=48), TCGA (n=59), Basel (n=32) and Karmanos (n=11) cohorts. ATX recurrence scores were generated using a locked model. 43 patients (Basel and Karmanos cohorts) also had ODX RS available. Prognostic performance of ATX and ODX RS was assessed for disease-free interval (DFI) endpoint using Harrell’s C-index and hazard ratio (HR per 0.1 increase in ATX). Reported HR and C-index are pooled using random-effects meta-analysis. Results: In a univariate model, ATX was a significant predictor of DFI in premenopausal N+ women with a hazard ratio of 2.77 (1.53-5.01, p=0.02) and C-index of 0.78 (95% CI: 0.64-0.92). ODX did not reach statistical significance with a HR of 1.05 (1.00-1.10, p=0.05) and C-index of 0.46 (0.32-0.59). In multivariate analysis adjusting for age, tumor size and grade, ATX was the only variable significantly associated with DFI (p<0.01). The estimated 5-year recurrence rates for ATX bottom and top quartiles were 9.1% and 25.7%. When divided into exploratory low/high ATX risk groups with threshold at 10% 5-year risk of recurrence (RoR), the ATX <10% RoR group included 39 patients with an observed recurrence rate of 5%, while ATX ≥ 10% RoR included 111 patients with an observed recurrence rate of 16%. Conclusions: ATX demonstrates promising independent prognostic performance in premenopausal node-positive breast cancer across diverse datasets. Larger studies are needed to confirm its efficacy and utility. Citation Format: J. Elayoubi, K. Choucair, K. Kalinsky, K. Pogoda, F. J. Esteva, K. Zeng, J. Cappadona, B. Machura, K. J. Geras, J. Witowski. Prognostic performance analysis of artificial intelligence test and 21-gene assay in premenopausal node-positive HR+ HER2- breast cancer patients [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-06-17.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are the standard of care in advanced breast cancer. While Ki67 is prognostic in early-stage disease, including adjuvant CDK4/6i, its role in metastatic setting is unclear. This study assessed Ki67’s prognostic value in advanced breast cancer treated with CDK4/6i. We conducted a retrospective analysis of patients with advanced breast cancer receiving CDK4/6i at our cancer center between 2018 and 2023. The study included 368 patients with Ki67 results. The median age was 63 years (IQR 52–70.5). 283 patients (76.9%) received CDK4/6i in the first-line. With respect to biopsy timing, Ki67 expression was evaluated in tissue samples from 319 patients in the metastatic setting and 49 patients in the early breast cancer setting. In terms of biopsy site, Ki67 was measured from the breast tumor in 235 patients, from regional lymph nodes in 26 patients, and from various metastatic sites in 107 patients. Ki67, as a continuous variable, correlated with PFS and OS. Specifically, each unit increase in Ki67 was associated with a 1% reduction in PFS and OS. Median PFS in patients with lowKi67 was 33.0 months vs. 22.0 months for highKi67 (p = 0.008). Two-year PFS was 68.3% for lowKi67, vs. 48.4% for highKi67. Median OS was 49.7 months for lowKi67 vs. 39.8 months for highKi67 (p = 0.027). Ki67 appears to be a prognostic factor in advanced breast cancer patients treated with CDK4/6i. Patients with low Ki67 had favorable prognosis.

Abstract Recurrence scores based on a 21-gene assay are clinically useful for predicting prognosis and chemotherapy benefit in postmenopausal node-positive breast cancer patients, but its performance in premenopausal patients is inconsistent. Here, we evaluated Ataraxis Breast RISK (ATX), an AI test that predicts recurrence risk, and compared it with the genomic assay. ATX identified high risk patients misclassified as low risk by the genomic assay and therefore may refine selection of patients for adjuvant chemotherapy.

Abstract Abstract Molecular mechanisms underlying congenital neutropenia in patients with HAX1 deficiency are not clear at the moment. HAX1 deficiency was shown to result in the arrest of neutrophil differentiation. Our studies of the effect of HAX1 deficiency on the proteomic and metabolic profiles of promyelocytic cells have led to the conclusion, supported by specific tests, that fatty acid metabolism is affected in HAX1 KO cells. The lipid droplet content is increased in HAX1 KO cells, pointing to the accumulation of fatty acids that are not metabolized. Studies of autophagosome function in HAX1 WT and KO cells revealed that lipid droplet autophagy is defective at the stage of fusion with the lysosome. Autophagy-dependent generation of free fatty acids is critical for neutrophil differentiation, so HAX1 deficiency that affects normal autophagy of lipids in promyeloblasts should explain differentiation arrest. Moreover, we have demonstrated that HAX1-deficient cells are also compromised in fatty acid uptake.